Modular engineering of Escherichia coli for high-level production of l-tryptophan / 生物工程学报

As an essential amino acid, l-tryptophan is widely used in food, feed and medicine sectors. Nowadays, microbial l-tryptophan production suffers from low productivity and yield. Here we construct a chassis E. coli TRP3 producing 11.80 g/L l-tryptophan, which was generated by knocking out the l-tryptophan operon repressor protein (trpR) and the l-tryptophan attenuator (trpL), and introducing the feedback-resistant mutant aroGfbr. On this basis, the l-tryptophan biosynthesis pathway was divided into three modules, including the central metabolic pathway module, the shikimic acid pathway to chorismate module and the chorismate to tryptophan module. Then we used promoter engineering approach to balance the three modules and obtained an engineered E. coli TRP9. After fed-batch cultures in a 5 L fermentor, tryptophan titer reached to 36.08 g/L, with a yield of 18.55%, which reached 81.7% of the maximum theoretical yield. The tryptophan producing strain with high yield laid a good foundation for large-scale production of tryptophan.

Effect of needle-knife on chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis based on CircSERPINE2-miR-1271-5P-ERG axis / 中国针灸

OBJECTIVE@#To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA.@*METHODS@#Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group.@*RESULTS@#After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01).@*CONCLUSION@#Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.

Diagnostic value of magnetic resonance spectroscopy for intracranial space-occupying lesions / 中国辐射卫生

Objective To evaluate the value of magnetic resonance spectroscopy (MRS) in the diagnosis of intracranial space-occupying lesions. Methods A total of 126 patients with intracranial space-occupying lesions in the First Affiliated Hospital of Xinjiang Medical University from 2019 to 2022 were enrolled and subjected to brain magnetic resonance imaging (MRI) and MRS examinations. The performance of MRI alone and in combination with MRS was evaluated and compared for diagnosis of intracranial space-occupying lesions. Results Tuberculoma (19.05%) and high-grade glioma (15.87%) were the intracranial space-occupying lesions most commonly diagnosed by MRI in combination with MRS. Radiologists confirmed the diagnosis of intracranial space-occupying lesions in 23.81% patients depending on MRI alone, and in 75.40% patients depending on MRI combined with MRS, with a 2.17-fold improvement (χ2 = 67.07, P<0.01). The combination of MRI and MRS improved the accuracy of imaging diagnosis of intracranial space-occupying lesions in 70 (55.67%) patients compared with MRI alone. In addition, MRI in combination with MRS significantly improved the accuracy of differential diagnosis of high-grade glioma, low-grade glioma, cerebral infarct, tuberculoma, recurrent tumor, and radiation necrosis compared with MRI alone (P<0.01). Conclusion The efficacy of imaging diagnosis of intracranial space-occupying lesions can be improved by MRI in combination with MRS relative to MRI alone. The combined use of MRI and MRS may serve as a non-invasive tool for diagnosis of intracranial space-occupying lesions. In addition, the combination facilitates the differentiation between low- and high-grade gliomas, between high-grade glioma and tuberculoma, and between recurrent tumor and radiation necrosis.

Quantitative susceptibility mapping of the substantia nigra subregions in relapsing-remitting multiple sclerosis patients / 中华放射学杂志

Objective:To investigate the distribution of iron deposition in the substantia nigral (SN) subregions on quantitative susceptibility mapping (QSM) and the change of swallow tail sign (STS) in patients with relapsing-remitting multiple sclerosis (RRMS) of different disease stages.Methods:The clinical and imaging data of 53 patients with RRMS (case group) diagnosed at the First Hospital of Chongqing Medical University from November 2019 to December 2021 were retrospectively analyzed. The case group was divided into 0-5 years subgroup, 6-10 years subgroup, and >10 years subgroup according to the disease duration; another 37 age-and gender-matched healthy volunteers were recruited as the control group during the same period. All subjects underwent MRI and QSM reconstruction. First, the SN was divided into four subregions: rostral anterior-SN (aSNr), rostral posterior-SN (pSNr), caudal anterior-SN (aSNc), and caudal posterior-SN (pSNc) on the QSM, and the quantitative susceptibility value (QSV) of each subregion was measured, and then the STS of the SN was observed and scored on the susceptibility weighted imaging (SWI) generated by post-processing. ANOVA was used to compare the differences in the QSV of each subregion of SN among the groups, and the probability of abnormal STS was compared using the χ 2 test. Spearman′s test was used to analyze the correlation between the QSV of each subregion of SN and the STS score. Results:The differences in QSV of aSNr, pSNr, aSNc, and pSNc were statistically significant among the 0-5 years subgroup, 6-10 years subgroup,>10 years subgroup of RRMS patients and the control group ( P<0.05). The QSV of aSNr, pSNr, and aSNc in 0-5 years subgroup was higher than those in the control group ( P was 0.039, 0.008, 0.039, respectively). The QSV of aSNr, aSNc, and pSNc in the 6-10 years subgroup were higher than those in the 0-5 years subgroup ( P was <0.001, 0.020, 0.015, respectively). The QSV of the aSNc, pSNc in >10 years subgroup were lower than those in the 6-10 years subgroup ( P=0.037, 0.006). The QSV of aSNr, pSNr in >10 years subgroup were higher than those in the control group ( P was <0.001, 0.001). There were 7 cases of abnormal STS in the 0-5 years subgroup, 11 cases in the 6-10 years subgroup, 12 cases in >10 years subgroup, and 9 cases in the control subgroup, and there was a statistically significant difference in the probability of abnormal STS among the subgroups of the RRMS patients and the control subgroup (χ 2=16.20, P=0.011). Both the scores of STS in the 6-10 years subgroup and >10 years group were positively correlated with the QSV in pSNc ( r s=0.65, P=0.006; r s=0.48, P=0.045). Conclusions:In RRMS patients, SN iron deposition is concentrated on aSNr, pSNr, and aSNc in the 0-5 years subgroup and on aSNr, aSNc and pSNc in the 6-10 years subgroup. The QSVs of all SN subregions have a downward trend in >10 years subgroup compared with that in the 6-10 years subgroup. Both the QSVs of the pSNc in the 6-10 years group and >10 years group are positively related to STS scores. These help explore the potential progression pattern of SN iron deposition in RRMS patients and the cause of abnormal STS in RRMS patients.

Quantitative analysis of demyelination and remyelination in modified cuprizone mice model based on T 2WI combined with DTI using 7.0 T MR / 中华放射学杂志

Objective:To explore the method of establishing a modified demyelination and myelination regeneration model induced by dicyclohexanone oxalyl dihydrazone (CPZ) in mice with multiple sclerosis (MS), and to analyze the image markers of demyelination and myelination regeneration in mouse MS model.Methods:After the intragastrically administered with sodium carboxymethyl cellulose (CMCNa) for one week, a total of 30 C57BL/6 male mice were randomly divided into the control group ( n=10), the demyelination group ( n=10), and the remyelination group ( n=10). The mice of the control group were immediately performed MR scanning and pathological specimen obtaining; the mice in the demyelination group were administered with intragastrical CPZ-CMCNa once a day for 6 weeks for inducing demyelination, then received MR scanning and specimen obtaining with the same protocols used in control group; the mice in the remyelination group were administered with intragastrical CPZ-CMCNa once a day for six weeks for demyelination, then CPZ was withdrawn and normal diet was given for another four weeks. Then MR scanning and specimen obtaining were performed with the same protocols used in the other two groups. Regions of interest (ROIs) were set at the rostrum of corpus callosum (rCC), the bilateral normal appearing white matters (NAWM) of the rostrum of corpus callosum, and the bilateral cerebral cortex (Cx). The normalized T 2WI (T 2-normalized), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were compared among the three groups by one-way ANOVA. Results:The demyelination and remyelination mice model of MS were successfully established. The T 2-normalized values of rCC in control group, demyelination group and remyelination group were 0.47±0.03, 0.72±0.04, 0.54±0.04, respectively, with statistically significant difference found ( F=90.511, P<0.05). Post-hoc multiple comparisons showed significant differences among those groups ( P<0.05). There was no significant difference of T 2-normalized value in NAWM and Cx among the three groups ( P>0.05). Moreover, there were significant differences in the FA values (0.36±0.04, 0.29±0.03, and 0.32±0.05), the MD values [(0.572±0.015), (0.598±0.034), and (0.626±0.043)×10 -3 mm 2/s], the AD values [(0.79±0.04), (0.77±0.06), and (0.83±0.04)×10 -3 mm 2/s], and the RD values [(0.46±0.02), (0.51±0.03), and (0.53±0.05)×10 -3 mm 2/s] of rCC of the control group, the demyelination group, and the remyelination group (all P<0.05). Significant difference was found in FA values between the demyelination group and the control group ( P<0.05), and in MD values between the remyelination group and the control group ( P<0.05), as well as in AD values between the remyelination group and the demyelination group ( P<0.05). There were also significant differences in RD values between the remyelination group and the control group, and the demyelination group and the control group (all P<0.05). However, no significant difference was found in all diffusion tensor imaging (DTI) metrics of NAWM and Cx among the three groups (all P>0.05). The LFB-eosin staining showed that the myelin sheath of rCC was lost in the demyelination group, and the rCC was partially regenerated and repaired in the remyelination group. Conclusion:The modified CPZ-CMCNa model can selectively induce demyelination and remyelination of rCC, and the changes of demyelination and remyelination of rCC in the modified CPZ-CMCNa model can be quantitatively detected by T 2WI combined with DTI, which might provide related theoretical basis for the study on dynamic changes of MS lesions.

Di (2-ethylhexyl) phthalate Disorders Lipid Metabolism via TYK2/STAT1 and Autophagy in Rats / 生物医学与环境科学（英文）

OBJECTIVE@#Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy.@*METHODS@#In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected.@*RESULTS@#The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism.@*CONCLUSION@#It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.

Effect of CTGF siRNA on Apoptosis of Fibroblast-like Synoviocytes of Rheumatoid Arthritis / 中国医科大学学报

Objective To silence the expression of CTGF by small interfering RNA technology,to observe the influence on fibroblast?like synovial cell apoptosis and several apoptosis?related genes,and to explore the mechanism of action of CTGF in rheumatoid arthritis synovial lesions. Methods Effective CTGF siRNA was screened through real?time PCR. The influence of CTGF siRNA on FLS apoptosis was detected with FITC?PI double staining by flow cytometry. bax,bcl?xl and survivin were detected using real?time PCR when CTGF mRNA has been silenced. Results Compared with other 2 groups of oligo and NC oligo,H1 oligo exhibited the strongest interfering action to CTGF(inhibition ratio>70%),so that it is selected as the effective target gene sequence for the following experiment. Apoptosis of FLS induced by serum deprivation was significantly decreased in the presence of exogenous CTGF. When expression of the CTGFgene was knocked down in FLS,FLS apoptosis was significantly increased,and expres?sion levels of survivin mRNA were decreased significantly(P<0.01). Conclusion FLS survival is positively regulated by CTGF,which may through the sustaining the expression of survivin.

The primary study on multi-b-value DWI in diagnosis of aypical infectious diseases in liver / 实用放射学杂志

Objective To discuss the value of the multi-b-value diffusion weighted imaging (DWI)in diagnosis of liver tuberculosis,abscess and atypical hydatid disease.Methods 23 patients with different liver lesions including abscess in 1 1,tuberculosis in 3 and alveolar hydatid in 9 were scanned with conventional MRI and multi-b-value DWI,and the imaging results were retrospectively analyzed.The ADC1 0b maps with 10 b values,three ADClow ones with low b values of 0 s/mm2 ,50 s/mm2 and 100 s/mm2 ,three ADChigh ones with high b values of 500 s/mm2 ,750 s/mm2 and 1 000 s/mm2 were gotten respectively.The ADCperf value was defined as a difference between ADClow and ADChigh values.Two regions of interest (ROI)with the same size were drawn in the liquefied region and mar-ginal area of the mass.The ADC values of ADClow ,ADChigh ,ADCperf and ADC1 0b maps were calculated and analyzed.Differences in b value and region among the three liver diseases were compared.Results The differences in ADC10b and ADChigh values between atypical liver hydatid and liver abscess in the liquefied region and marginal area were significant (P 0.05).No differences in the ADClow value were found in both areas of three lesions (P >0.05). Conclusion Multi-b-value DWI and ADC maps and ADC values can provide valuable information in diagnosis and differentiation of liver tuberculosis,abscess and atypical hydatid disease.Different ADC values play more important role in the diagnosis of liver diseases.

A PCR-based Rapid Neutralization Assay for GII.4 Norovirus Infection in HIEC6 Cell Culture / 生物医学与环境科学（英文）

Because of limited viral replication and lack of cytopathic effect in cell culture, a new PCR-based rapid seroneutralization assay for detection of GII.4 norovirus neutralized antibodies was developed with serum samples from acute-phase patients, convalescent-phase patients and healthy controls. According to this study, neutralizing antibodies were detected in 100% of convalescent-phase sera, and in 2.5% of healthy controls sera. However, all of the acute-phase serum samples could not neutralize virus efficiently. Compared to the results from ELISA (96.2% at sensitivity and 80% at specificity), the present in vitro neutralization assay is more specific and more sensitive.

Changes of glial cells and white matter in pubescent stage of schizophrenia rats / 中华行为医学与脑科学杂志

Objective To explore the changes of pubescent immune response in the schizophrenia offspring induced by poly(I:C) during pregnancy and the effects on white matter.Methods The obtained pregnant rats were randomly divided into model group(n=6) and control group (n=5), receiving either poly (I:C) at a dose of 10 mg/kg diluted in 0.9％ NaC1 solution or vehicle solution alone (sterile pyrogen-free 0.9％ NaC1) on gestation day 9 (GD9).Immunohistochemical technique(IHC) was applied to detect the changes of microglias and astrocytes in the prefrontal cortex(PFC) and hippocampus(HC) of partly offsprings in the two groups at the sixth week,as well as Luxol fast blue(LFB) for the changes of white matter.The other offsprings of each group were selected for behavioral assessment at the eighth week.Results The results of prepulse inhibition test showed that PP2, PP4 and PP8 of model groups were significantly lower than that of the control group at young adult(P＜0.01).In passive avoidance test, and the T1 results of model group were significantly higher than those of the control group, the T results of model group were lower than those of control group (P＜ 0.01).Immunohistochemical results indicated that the number of microglias in the model group((264±33)/mm2, (271 ±38)/mm2) was significantly increased in PFC and HC than that in the control group((140±29)/mm2, (169±37)/mm2, P＜0.05) ,which was accompanied with significant morphological changes, while the OD value of astrocyte protein expression in the frontal lobe and hippocampus had no obvious difference between the model group and control group(P＞0.05).The OD value of LFB staining for myelin in the model group(0.29±0.02) was significantly decreased compared with that in the control group(0.33±0.03)(P＜0.01).Conclusion The young adult offsprings with prenatal infection present obvious schizophrenia-like behavior, meanwhile, the microglias activation and demyelination changes in white matter are observed,which provides more evidence for the relationship between immune response and white matter in the pathogenesis of schizophrenia.

Value of targeted MR molecular imaging in evaluating the early efficacy of anti-angiogenesis drugs / 中华放射学杂志

Objective To assess the value of noninvasive MR imaging biomarkers in evaluating the early efficacy of anti?angiogenesis drugs. Methods Subcutaneous colon cancer xenograft models in thirty nude mice were established. The mice were randomly divided into three groups (n=10 for each): avastin injection group (dose 10 mg/kg), fluorouracil group (dose 150 mg/kg), physiological saline group (dose 20 mg/kg). Dynamic contrast?enhanced (DCE?MRI) and multiple b value diffusion weighted imaging (muti?b?value DWI) were acquired before or 1 h, 24 h and 48 h after the treatment. The parameters of contrast transfer coefficient (Ktrans), reflux constant (Kep), plasma volume fraction (Vp), extravascular extracellular volume fraction (Ve) and various apparent diffusion coefficients (ADCs) (ADC10b, ADChigh and ADCperf) were measured. Forty eight hours after the treatment, the mice were sacrificed following MRI. Aimmunohistochemical examination determined microvessel density (MVD) and proliferating cell nuclear antigen (PCNA) score. A repeated measures analysis of variance was used to compare the difference between the quantitative parameters among the three groups. A multivariate variance analysis was performed to compare the difference between the parameters at the same time point among the three groups. The correlation between MRI quantitative parameters with MVD and PCNA score were analyzed by Pearson and Spearman correlation analysis respectively. Factor analysis method summarized MRI quantitative parameters. Results One hour after the treatment, the parameters of Ktrans, Kep, ADC10b, ADChigh and ADCperf value immediately changed, they were(0.009 ± 0.005)/s,(0.042 ± 0.031)/s,(0.043 ± 0.002)× 10?3 mm2/s,(0.031 ± 0.005)× 10?3 mm2/s,(0.089 ± 0.006)× 10?3 mm2/s, Ktrans, Kep, ADC10b and ADChigh values all had significant differences in the three groups (F=42.058, 25.979, 9.870 and 8.511, respectively, all P<0.05). There were also statistical difference in the change trend of the above parameters among the three groups (F=22.108, 7.280, 65.698 and 19.900, respectively, all P<0.05). The change trend of ADCperf showed significant difference among the three groups (F=38.780, P<0.01). Ktrans, Kep and ADCperf positively correlated with the MVD count and PCNA score (r values were 0.421 to 0.811, both P<0.01), while ADC10b showed a negative correlation (r=-0.656 and-0.560, both P<0.01), ADChigh had negative correlation with the PCNA score (r=-0.568, P<0.05). Ktrans, Vp, Kep and ADCperf were classified as tumor microcirculation factor, whereas ADC10b and ADChigh were normalized for cell metabolism factor through the factor analysis. Conclusions Combination of DCE?MRI and muti?b?value DWI can reflect the early changes of drug therapy from the aspects of tumor microcirculation and cell metabolism. Ktrans, Kep, ADCperf, ADC10b and ADChigh can be taken as noninvasive imaging biomarkers to quantify the early efficacy of anti?angiogenesis drugs.

Value of MR diffusion weighted imaging in assessing the viability of hepatic alveolar echinococcosis / 中华放射学杂志

Objective To evaluate DWI in the assessment of viability of hepatic alveolar echinococcosis (HAE) by comparing DWI with PET-CT results. Methods 18-fluorodeoxy glucose(18F-FDG) PET-CT and DWI(b values=0, 800 s/mm2) were retrospectively analyzed in 8 patients with clinically verified HAE. The metabolic activity of HAE lesions in both techniques were determined by two independent radiologists respectively. Kappa test was assessed between the results of two observers. Results Sixteen lesions (composed of 14 HAE and 2 cystic echinococcosis, CE) were detected. (1)Eight lesions (≥2 cm) showed perilesional hyper-signal intensity on DWI, mainly around the lesion bounding by normal liver parenchyma. One patient (≥2 cm) had oral drug therapy for three years, and the lesion showed discontinuous perilesional hyper-signal intensity on DWI after the therapy. Five lesions (<2 cm) were depicted as nodular high signal on DWI.(2)Eight lesions (≥2 cm) showed perilesional increased FDG uptake on PET-CT, while 5 lesions (<2 cm) displayed as“hot pot”. One patient (leison≥2 cm) who had oral drug therapy for three years showed hepatic defect without any FDG uptake in post-treatment PET-CT. Two CE lesions showed negative results on both DWI and PET-CT. The Kappa value of 0.880 indicated a good coincidence between DWI and PET-CT in depicting the metabolic activity of HAE (P=0.006). Conclusions This preliminary study showed the value of DWI in assessing HAE viability. DWI should be routinely used as one of the techniques in the evaluation of HAE.

Experimental study on early effects of bevacizumab evaluated by dynamic enhanced magnetic resonance imaging / 中华消化杂志

Objective To explore the feasibility and value of dynamic contrast-enhanced (DCE-MRI) parameters in assessing early effects of anti-angiogenesis medicine in targeted therapy for tumors.Methods Twenty BALB/C-nu nude mice were injected subcutaneously with human colon cancer cells HT-29 to the right hind leg.The nude mice were evenly divided into the experimental group and control group with 10 mice in each group.The mice of experimental group were intraperitoneally injected with bevacizumab,and the control group were injected with the same volume of saline.DCE-MRI was performed before medication and one hour,24 h and 48 h after medication.The Ktrans,Kep,Ve and initial area under enhancement curve (iAUC) of DCE-MRI were analyzed.The animals were sacrificed 48 hours after medication.Microvessel density (MVD) of the tumors was detected by immunohistochemistry.One way analysis of variance was performed to analyze parameters of DCE-MRI.The Pearson correlation coefficient was used to analyze the correlation between parameters of DCE-MRI and MVD.Results Under DCE-MRI,the edge of subcutaneous colon cancer xenografts was obviously gradually enhanced,pseudo color indicated high perfusion,the strength degree of the central region was low and which meant low perfusion.The differences in Kep of different time point of experimental group were statistically significant (F=3.752,P=0.016) ; there as no significant difference in other parameters of DCE MRI (all P＞0.05).There was no significant difference in Ktrans and Kep before medication and one hour after medication (all P＞0.05).There were significant difference in Ktrans and Kep 24 hour and 48 hour after medication between experimental group (24 hour∶ (0.095 ± 0.039) min-1 and (0.297 ± 0.141) min-1,48 hour∶ (0.090±0.033) min 1 and (0.314±0.148) min-1) and control group (24 hour∶ (0.150±0.074) nin-1 and (0.494±0.126) min-1,48 hour∶ (0.171±0.045) min-1 and (0.441± 0.092) min-1) (F24h =4.824 and 11.386,F48h =22.605 and 5.455,all P＜0.05).There was no significant difference in Ve and iAUC between two groups at different time points (all P＜0.05).MVD of experimental group was lower than that of control group.Ktrans and Kep were positively correlated with MVD (r=0.745 and 0.400,both P＜0.05).Conclusion Ktrans and Kep parameters of DCE-MRI may be used in monitoring the earlier effects of anti-angiogenesis medicine in targeted therapy for colon cancer.

Start-up of a full-scale system for short-cut nitrification and Anammox in treatment of pharmaceutical wastewater / 生物工程学报

In order to broaden the application area of the new nitrogen removal technology, a full-scale system for short-cut nitrification and anaerobic ammonium oxidation (Anammox) was investigated in the nitrogen removal from a strong-ammonium pharmaceutical wastewater. When the influent ammonium concentration was (430.40 ± 55.43) mg/L, ammonia removal efficiency was (81.75 ± 9.10)%. The short-cut nitrification and Anammox system could successfully remove nitrogen from the pharmaceutical wastewater. The start-up of short-cut nitrification system took about 74 d and the nitrite accumulation efficiency was (52.11 ± 9.13)%, the two-step mode using synthetic wastewater and actual wastewater was suitable for the start-up of short-cut nitrification system. The start-up of Anammox system took about 145 d and the maximum volumetric nitrogen removal rate was 6.35 kg N/(m3·d), dozens of times higher than those for the conventional nitrification-denitrification process. The strategy achieving Anammox sludge by self-growth and biocatalyst addition was suitable for the start-up of Anammox system.

Studies on the cognitive behavior and the myelin basic protein of the offspring in adult by infecting polyriboinosinic-polyribocytidilic acid in pregnacy / 中华行为医学与脑科学杂志

Objective By analyzing the changes in behavior and the myelin basic protein (MBP) of the offspring in adult that treated with Poly(I∶C) during pregnancy,and to understand the role of white matter abnormalities in the abnormal behavior of the offspring induced by infection in maternal hosts.Methods Two models maternal female rats were given Poly(I∶ C) with 5 mg/kg and 10mg/kg respectively during the early pregnancy,and control maternal female rats was administered 5 mg/kg saline.The prepulse inhibition test,passive avoidance test and active avoidance test were used to evaluate schizophrenia like behaviors for each groups offspring in 8 weeks,and the expression of MBP was detected by immunohistochemical staining methods.Results The results of prepulse inhibition test showed that significant differences of PP2,PP4 and PP8 results existed among control group,single-dose model group and double-dose model group (F=10.381,P=0.001,F=10.313,P=0.001,F=15.233,P=0.000).Compared with the control group,the two model groups showed significantly lower,the double-dose model group was lower than single-dose model group (P＜0.05).In passive avoidance test,there were significant differences of T1 and T2 results existed among control group,single-dose model group and double-dose model group (F=23.555,P=0.000,F=17.524,P=0.000).The T1 results of two model groups were significantly higher than control group,the double-dose model group was significantly higher than single-dose model group (P＜0.05) ; the T2 results of two model groups were lower than control group,the double-dose model group was lower than single-dose model group(P＜0.05).The results of passive avoidance test indicated that significant differences existed among control group,single-dose model group and double-dose model group in whole period of testing and total conditioned response rate(F=8.631,P=0.000,F=6.986,P=0.001),the two model groups were significantly lower than control group,double-dose model group was significantly lower than single-dose model group (P＜0.05).MBP results of two model groups were significantly lower than control group,two model groups had no significant difference (P＞ 0.05).Conclusion The adult offspring that were treated with Poly (I∶C) exit abnormal behavior and damaged white matter,and there is a correlation between the degree of abnormal behavior and drug dose.

Clinical and laboratory investigation of pericentric inv(9)(p22q34) with the der(9)t(9;22)(q34;q11) in Ph-positive leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate clinical and molecule genetics features of four Ph-positive leukemia patients characterized by pericentric inv(9)(p22q34) with the der(9)t(9;22)(q34;q11).</p><p><b>METHODS</b>Cytogenetic analysis was carried out on bone marrow directly or after short-period culture. R banding was used for karyotype analysis. BCR/ABL fusion gene was detected with interphase fluorescence in situ hybridization (FISH), and chromosome painting was carried out using specific probes. RT-PCR was used to detect BCR/ABL chimeric transcripts.</p><p><b>RESULTS</b>One patient with acute myeloid leukemia (AML) presented three clones, which included one with a normal karyotype, one with t(9;22)(q34;q11), and one with inv(9)(p22q34) involving the der(9)t(9;22) and additional t(8;12)(q12;p11). The inv(9)(p22q34) has always co-occurred with der(9)t(9;22)(q34;q11) accompanied by der(22)t(9;22)(q34;q11) in all metaphases from the three patients with chronic myeloid leukemia (CML). B3a2 transcript was detected in all patients by RT-PCR. Inv(9)(p22q34) was found in both CML and AML, and was associated with poor prognosis.</p><p><b>CONCLUSION</b>Inv(9)(p22q34) is a novel, rare, but recurrent secondary chromosomal abnormality for Ph-positive leukemia. Leukemia with der(9)t(9;22) and inv(9)(p22q34) has unique clinical and laboratory characteristics.</p>

The efficacy and impact of recombinant human cytotoxic T lymphocyte-associated antigen-4 fusion protein on human tumor necrosis factor-α and CX3CL1 in active rheumatoid arthritis patients / 中华风湿病学杂志

Objective To evaluate the efficacy,safety and impact of recombinant human cytotoxic T lymphocyte-associated antigen (CTLA)-4 fusion proteins (rhCTLA-4Ig) on serum human tumor necrosis factor (TNF)-α and CX3CL1 in active rheumatoid arthritis (RA) patients.Methods Forty-four RA patients were treated with rhCTLA-4Ig and placebo.Clinical response was assessed by American College of Rheumatology (ACR) criteria and disease activity score in 28 joints (DAS28).The levels of serum TNF-α and CX3CL1 were determined in 44 RA patients and 20 healthy controls by enzyme-linked immunosorbent assay (ELISA).Comparisons between groups were performed by t-test or x2 test.Results At week 12,ACR20,ACR50and ACR70 responses in RA patients with rhCTLA-4Ig were achieved by 95％(20/21 ),76％( 16/21 )and 19％(4/21) respectively,but no patient with placebo achieved ACR20,ACRS0 and ACR70 responses.There were significantly statistical differences in ACR20 and ACR50 responses (x2=39.17,26.69,P＜0.01 ).At week 12,the mean DAS28 in the rhCTLA4Ig group was 3.1±1.3 versus 6.2±1.1 at baseline (P＜0.01).Similarly,health assessment questionnaire (HAQ) improved significantly,declining from 1.4±0.5 at baseline to 0.4±0.5 at week 12 (P＜0.01).However,the mean DAS28 in the placebo group was 5.8±1.2 versus 6.0±0.7 at baseline (P＞0.05),HAQ declined from 1.6±0.4 to 1.6±0.6 (P＞0.05).In addition,there were higher levels of TNF-α and CX3CL1 in the active RA patients than those of the healthy controls (P＜0.01).After 12 weeks therapy,Serum TNF-α and CX3CL1 levels in the rhCTLA-4Ig group decreased significantly (P＜0.01).There weren't decline in the placebo group (P＞0.05).Conclusion This study has shown that rhCTLA-4Ig is very effective in reducing disease activity,improving function during the 12 weeks treatment.rhCTLA-4Ig therapy for 12 weeks can lead to significant decrease of serum TNF-α and CX3CL1.

Performances of anammox-EGSB bioreactors started up with three different seeding sludges / 生物工程学报

In order to select better seeding sludge and promote start-up of Anammox reactors, we studied the start-up performances of three Anammox-EGSB bioreactors inoculated with anaerobic methanogenic sludge (AMS) (R1), Fresh Anammox sludge (FAS) (R2) and stored Anammox sludge (SAS) (R3), respectively. Results showed that these three seeding sludges could start up Anammox-EGSB bioreactors successfully, but the start-up progresses showed different characteristics. The start-up course of R1 could be divided into three phases including autolysis phase (15 d), lag phase (54 d) and activity elevation phase (40 d). However, the start-up courses of R2 and R3 only included lag phase (2 d and 12 d, respectively) and activity elevation phase (15 d and 57 d, respectively). Besides, the performance of R3 was better than that of R1, but worse than that of R2. Furthermore, bathing the Anammox sludge in the effluent of bioreactors was a convenient and effective way to keep the activity of the Anammox sludge. The ammonia removal efficiency, percentage of denitrification and the stoichiometric ratios of NH4(+)-Nr/NO2(-)-Nr and NO3(-)-Np/NH4(+)-Nr could serve as indicators to monitor the start-up of Anammox bioreactors.

Cerebral activation during Chinese semantic associative task in Xinjiang' Uyghurs: a functional MRI study / 中华放射学杂志

Objective To explore the cerebral activation in Xinjiang' Uyghurs when performing a Chinese word tasks by the functional magnetic resonance image (fMRI).Methods Twenty-one healthy Xinjiang' Uyghurs and 11 healthy Hans were scanned using functional magnetic resonance imaging (fMRI) on a 1.5 T MRI scanner with a single run.Different Chinese words were displayed in each block to avoid any practice effect SPM5.0 software was used for image data processing.To evaluate the inter subject consistency of brain activations associated with Chinese character and word reading, we created penetrance maps by combining binary individual functional maps.Results For Uyghur-Chinese bilingual subjects, activations related to generated a word that was semantically related to each stimulus.The results indicated that reading Chinese is characterized by extensive activity of the neural systems.Peak activations occurred in the left middle frontal cortex at Brodmann Areas (BA9 and BA 47).The left temporal (BA 37) cortices were also strongly activated.Other important activated areas included bilateral visual systems (BA 17-19) and cerebellum.The location of peak activation in the left frontal regions was similar in Native Uyghurs and Hans.But the active areas in Uyghurs are more extensive than that of Hans .Conclusions The location of peak activation in the left frontal regions was similar in Native Uyghurs and Hans.More brain areas were needed for Xinjiang' Uyghur speakers during processing Chinese words.

Injury of bone marrow endothelial niche by irradiation myeloablative conditioning in mouse allo-BMT / 中国实验血液学杂志

The aim of study was to investigate the injury of bone marrow microenvironment after γ ray irradiation conditioning in mouse allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mononuclear cells collected from mice bone marrow for culture in vitro, were identified by flow cytometry with double staining when cultured for 5 - 7 days. Mice were separated randomly into 4 groups, namely, the control group, irradiation group, endothelial progenitor cell (EPC) transplantation group and irradiation combined EPC transplantation group. Peripheral blood was collected to assay the circulating white blood cells. The histological, electron microscopic and immunofluorescence analyses of bone marrow were performed in the same time, furthermore the distribution of labeled EPC was determined. The results showed that EPC were identified as CD45(low/-)CD133(+)CD31(+), double positive of Dil-Ac-LDL and FITC-UEA-1. The bone marrow microenvironment injury of recipient mice was shown in the irradiation group in which the number of WBC began to decrease after conditioning, and the mice were all died at 8 days (p < 0.05). The intramedullary hemorrhage could be detected by light microscopy at 3 days after irradiation, when the destruction of connection between endothelial cell and the basement membrane was observed by TEM. There were CFSE labeled cells in bone marrow in irradiation combined EPC transplantation group at 18 hours after transplanted cultured EPC in vitro, the number of CFSE(+) cells was 58-folds of EPC transplantation group (p < 0.05). It is concluded that the irradiation can cause the severe endothelium injury that drives extrinsic EPC homing to the injured bone marrow microenvironment.